Given the extensive morbidity and mortality associated with injury and sudden cardiac death, evaluation of innovative therapies is warranted. The reduction of mortality and improvement of functional outcomes through early application of therapies in the out-of-hospital setting is promising. The time-dependent nature of resuscitation from both life-threatening injury and sudden cardiac death requires that evaluation of potential interventions in both of these disease states incorporate the Emergency Medical Services (EMS) system. Successful scientific investigation of proposed prehospital resuscitation interventions mandates a mature EMS system with the following features: effective integration with state-of-the-art hospital care; established collaborative relationships between out-of-hospital personnel and hospital-based investigators; and comprehensive, prospective data collection beginning in the out-of-hospital setting and ending with postdischarge longitudinal outcomes. This proposal summarizes the extensive EMS research experience of the multidisciplinary Emergency Prehospital Investigative Consortium (EPIC) team and details how the community and EMS agencies affiliated with the EPIC team meets the goals of this ideal EMS investigative environment. The specific aims of this proposal are as follows: -To use the EMS and hospital-based research infrastructure in the Portland Metropolitan Area and surrounding region to carry out advanced interventional resuscitation research on victims of major trauma and of cardiac arrest as part of the EPIC trial; -To conduct a randomized, controlled trial studying the efficacy of hypertonic saline in moderate to severe traumatic brain injury; and - To conduct a randomized, controlled trial studying the use of vasopressin versus epinephrine in out of-hospital cardiopulmonary arrest. - To describe a Research Skills Training Core that will foster the development of clinical researchers who will address future EMS and trauma/cardiac resuscitation concerns.